A lignan compound represented by formula I: wherein,                R0 is a hydrogen or a hydrophilic group;        R1 is a lower alkyl group which may be substituted, a cycloalkyl group which may be substituted, a cycloalkyl lower alkyl group which may be substituted, an aryl group which may be substituted, an aralkyl group which may be substituted, a heterocycle which may be substituted;        R′ is a lower alkyl group which may be substituted or an aralkyl group which may be substituted; and        R4, R5, R6, R7 and R8 are each a lower alkyl group and salts thereof are known to be useful in various clinical uses, particularly, as an antihyperlipidemia drug or a bile acid reabsorption inhibiting drug (Japanese Patent Publication (not examined) No. 241206/1997). The present inventors have found that a lignan compound represented by the following formula II, which is a member of the above formula I, is particularly useful as a medicament. However, this compound is not crystalline, and therefore, in an industrial production thereof, it has been necessary to conduct column chromatography for several times in order to purify the compound. Moreover, the yield of the compound has been low for this reason. The above Japanese Patent Publication (not examined) No. 241206/1997 does not describe an amine salt in terms of a salt of a compound of formula I.Problems to be Solved by the Invention        
In an industrial mass production aiming at use as a medicament of the compound represented by formula II: i.e., [1-O-[4-(3,4-dimethoxyphenyl)-2-(3-ethylpentanoyl)-5,6,7-trimethoxy-3-(methoxycarbonyl)naphthalen-1-yl]-beta-D-glucopyranoside]uronic acid (glucuronate conjugate), it was very inconvenient that column chromatography had to be conducted in order to purify the compound, and therefore, development of a simple method for the purification of the compound has been desired.Means to Solve the Problems
As a result of research for the purification of the compound of formula II, the present inventors have found that this compound can be crystallized by transforming into an amine salt thereof, and here, succeeded in purifying this compound efficiently by such crystallization. The present invention has been accomplished by this discovery. By transforming into an amine salt to be crystallized, the compound of formula II can be refined and easily isolated from a reaction mixture by means such as filtration. The amine salt of said compound isolated can be transformed easily into the free compound by treating with a dilute acid or the like.
Thus, the present invention provides                (1) An amine salt of [1-O-[4-(3,4-dimethoxyphenyl)-2-(3-ethylpentanoyl)-5,6,7-trimethoxy-3-(methoxycarbonyl)naphthalen-1-yl]-beta-D-glucopyranoside]uronic acid;        (2) The amine salt of (1) which is a diethylamine salt;        (3) The amine salt of (1) or (2) which is a crystal;        (4) The diethylamine salt of (3) which exhibits a powder X-ray diffraction pattern wherein the main peaks appear at 2θ=9.800, 13.760, 16.960, 17.100, 18.140 and 18.340 (degree);        (5) The diethylamine salt of (4) which exhibits a powder X-ray diffraction pattern wherein the main peaks appear at 2θ=8.820, 9.800, 13.760, 14.340, 14.540, 15.560, 16.960, 17.100, 18.140, 18.340, 19.560, 21.740, 22.040 and 22.280 (degree);        (6) A process for preparing [1-O-[4-(3,4-dimethoxyphenyl)-2-(3-ethylpentanoyl)-5,6,7-trimethoxy-3-(methoxycarbonyl)naphthalen-1-yl]-beta-D-glucopyranoside]uronic acid, which comprises purification thereof by transforming the acid into an crystalline amine salt;        (7) The process of (6) wherein said process does not comprise a treatment by means of column chromatography;        (8) A process for preparing [1-O-[4-(3,4-dimethoxyphenyl)-2-(3-ethylpentanoyl)-5,6,7-trimethoxy-3-(methoxycarbonyl)naphthalen-1-yl]-beta-D-glucopyranoside]uronic acid, which comprises a treatment of a crystalline amine salt thereof to form the free compound; and        (9) A pharmaceutical composition comprising the amine salt of any one of (1)-(5).        
For preparation of the amine salt of the invention, a crude product of the compound of formula (II) is dissolved in an appropriate solvent, for example, alcoholic solvents such as methanol, ethanol, or isopropyl alcohol, ether solvents such as THF, aromatic hydrocarbons such as toluene, or xylene. The resultant mixture is added with an amine to mix at a temperature between 0° C. and 100° C., preferably between room temperature and 70° C., and then optionally allowed to cool to a temperature between room temperature and 0° C. Crystals precipitated can be filtered out and washed with a solvent as described above. Diethylamine is preferable for use as an amine.
As described above, the resultant amine salt of the compound of formula II, can be treated easily with an acid, such as a dilute acid, to form the free compound.
As described above, the amine salt of the invention is useful as an intermediate, but itself may be used as an active ingredient. Accordingly, the present invention further provides a medicament, such as anti-hyperlipidemia drug, containing said amine salt. The amine salt of the invention may be a solvate, such as a hydrate or an alcoholate.
Best Mode for Carrying Out the Invention
The following examples further illustrate the present invention and are not intended to be limiting to the scope of the invention in any respect.